Friedreich's ataxia (FRDA) is a progressive degenerative disease that affects mainly the muscular system, the nervous system, and the heart. With an estimated prevalence of 1 in 50.000 individuals in the Caucasian population, it is the most common form of inherited ataxia (Harding, 1981; Campuzano et al., 1996). Symptoms are progressive and generally appear during puberty, although the age of onset varies from childhood (2-3 years) to adulthood (after 25 years). Gait instability and lack of coordination are the main symptoms of the disease. Additional symptoms include dysarthria, areflexia, sensory loss, skeletal abnormalities, and left ventricular hypertrophy, which is the main cause of cardiac failure and premature death.
FRDA is caused by a homozygous hyperexpansion of GAA triplets (from about 70 to about 1000 triplets) within the first intron of the gene coding for frataxin (FXN) (Marmolino, 2011). This type of mutation reduces transcription of the FXN gene due to the formation of ‘sticky’ DNA structures and epigenetic changes, while maintaining a minimal residual amount of frataxin (about 10-30%), which is essential for survival during embryonic development. Frataxin is involved in several mitochondrial activities, such as iron metabolism and regulation of iron-sulfur clusters (ISCs) assembly, ATP generation, and oxidative stress control. Though frataxin is expressed ubiquitously in the organism (Campuzano et al., 1997), its deficiency primarily affects some regions of the central and peripheral nervous system, heart, skeleton, and endocrine pancreas, causing the main clinical and pathological features of the disease (Koeppen and Mazurkiewicz, 2013). Currently, there is no approved treatment for FRDA. There is a need for novel and effective treatments for FRDA.